The objective of the proposed studies is to describe the physiological interaction between the autonomic nervous system and the heart with healed myocardial infarction, and the characterize the long-term alterations in neural activity which arise from acute cardiac ischemic injury. In pilot experiments, we delineated a disparate effect of bilateral sympathetic nerve stimulation on ventricular refractoriness in cat hearts with healed (greater then 2 months). A "halo" effect was noted, i.e., normal cells surrounding the infarct were most responsive to stimulation. We now extend our research to evaluate the consequences of acute ischemia on neural-cardiac interactions in the setting healed myocardial infarction. Six specific projects encompassing our specific aims are proposed concerning these subjects: (1) to characterize the refractoriness of ventricular muscle in hearts with acute or healed infarction during sympathetic or vagal nerve stimulation; (2) to determine whether refractoriness during sympathetic stimulation in these diseased hearts is modified by concomitant parasympathetic stimulation; (3) to establish whether ventricular refractoriness to autonomic stimulation is further modified by the formation of an acute infarction contiguous to a healed infarct; (4) to correlate the degree of dispersion of ventricular refractoriness during autonomic nerve stimulation with the occurrence of ventricular arrhythmias in both hearts with healed and acute-healed infarctions; (5) to study epicardial actionpotential characteristics in isolated ventricles with acute, healed or contiguous acute-healed infarction; (6) to develop the techniques for single unit nerve recording in animals with healed myocardial infarction. Bipolar electrodes monitor epicardial ventricular refractoriness in normal, border and infarct areas in the presence and absence of electrical activation of selected autonomic nerves. Microelectrodes monitor epicardial activity in tissue bath. Studies in normal and appropriate sham-operated animals provide control measurements. These data will contribute to our overall objective of understanding the electrophysiologic instability of diseased hearts, potentially lethal arrhythmias in humans and their therapy.